Acute Infection and Subsequent Subclinical Reactivation of Herpes Simplex Virus 2 after Vaginal Inoculation of Rhesus Macaques.

Herpes simplex virus 2 (HSV-2) is a common sexually transmitted infection with a highly variable clinical course. Many infections quickly become subclinical, with episodes of spontaneous virus reactivation. To study host-HSV-2 interactions, an animal model of subclinical HSV-2 infection is needed. In an effort to develop a relevant model, rhesus macaques (RM) were inoculated intravaginally with two or three HSV-2 strains (186, 333, and/or G) at a total dose of 1 × 107 PFU of HSV-2 per animal. Infectious HSV-2 and HSV-2 DNA were consistently shed in vaginal swabs for the first 7 to 14 days after each inoculation. Proteins associated with wound healing, innate immunity, and inflammation were significantly increased in cervical secretions immediately after HSV-2 inoculation. There was histologic evidence of acute herpesvirus pathology, including acantholysis in the squamous epithelium and ballooning degeneration of and intranuclear inclusion bodies in epithelial cells, with HSV antigen in mucosal epithelial cells and keratinocytes. Further, an intense inflammatory infiltrate was found in the cervix and vulva. Evidence of latent infection and reactivation was demonstrated by the detection of spontaneous HSV-2 shedding post-acute inoculation (102 to 103 DNA copies/swab) in 80% of RM. Further, HSV-2 DNA was detected in ganglia in most necropsied animals. HSV-2-specifc T-cell responses were detected in all animals, although antibodies to HSV-2 were detected in only 30% of the animals. Thus, HSV-2 infection of RM recapitulates many of the key features of subclinical HSV-2 infection in women but seems to be more limited, as virus shedding was undetectable more than 40 days after the last virus inoculation.IMPORTANCE Herpes simplex virus 2 (HSV-2) infects nearly 500 million persons globally, with an estimated 21 million incident cases each year, making it one of the most common sexually transmitted infections (STIs). HSV-2 is associated with increased human immunodeficiency virus type 1 (HIV-1) acquisition, and this risk does not decline with the use of antiherpes drugs. As initial acquisition of both HIV and HSV-2 infections is subclinical, study of the initial molecular interactions of the two agents requires an animal model. We found that HSV-2 can infect RM after vaginal inoculation, establish latency in the nervous system, and spontaneously reactivate; these features mimic some of the key features of HSV-2 infection in women. RM may provide an animal model to develop strategies to prevent HSV-2 acquisition and reactivation.

An unresponsive progressive pustular and crusting dermatitis with acantholysis in nine cats.

BACKGROUND: Between 2000 and 2012, nine cats were examined with a visually distinctive, progressive crusting dermatitis that was poorly responsive to all attempted therapies. OBJECTIVES: Documentation of clinical and histopathological findings of this disease. ANIMALS: Nine privately owned cats. METHODS: Retrospective study. RESULTS: Eight neutered males and one (presumably spayed) female ranging in age from two to eight years, presented for a progressive, well-demarcated, crusting dermatitis with variable pruritus of 1.5 months to five years duration. All cats lived in northern California, USA; seven lived within a 30 mile radius. Two males were littermates. Histopathological investigation showed both parakeratotic and orthokeratotic crusts, intraepidermal pustules and superficial folliculitis with rare to frequent acantholytic cells. Bacterial and fungal cultures were performed in six cats: meticillin-susceptible Staphylococcus pseudintermedius was isolated in three cats, two colonies of Trichophyton terrestre and three of Malassezia pachydermatis were isolated from one cat each. Treatment with various antibiotics, antifungal and a variety of immunosuppressive medications did not alter the progressive nature of the skin disease. CONCLUSIONS AND CLINICAL IMPORTANCE: The described disease shares some clinical and histopathological features with pemphigus foliaceus, but the lack of response to treatment, its progressive nature and the possible relatedness of some of the cats set it apart. The aetiology of this acantholytic dermatitis remains unknown.

Acantholytic folliculitis and epidermitis associated with Staphylococcus hyicus in a line of white Leghorn laying chickens.

Several mature Leghorn-type hens with the same genetic background experienced skin and feather problems in a breeder flock. There was almost-total feather loss on the head and neck, as well as thickened, scaly skin, and follicular ostia were plugged with keratin debris. Other individuals exhibited prominent subcutaneous nodules multifocally on the head. Histologic examination of the skin revealed a severe hyperplasia of follicular epithelium with hyperkeratosis and cystic dilation. Numerous clefts and vesicles were detected along the epidermis and follicular epithelium, some containing acantholytic keratinocytes. A mild heterophilic inflammation was associated with these lesions, and few gram-positive cocci were present in the keratin plugs. Bacterial culture of the skin yielded a variable amount of Staphylococcus hyicus. Immunochemistry looking for chicken IgY revealed no intercellular staining in the epidermis or follicular epithelium. All these findings supported a diagnosis of Staphylococcus-associated acantholytic epidermitis and folliculitis. This case suggests that S. hyicus could be a significant pathogen in poultry production. The close genetic relationship among affected individuals could indicate a hereditary predisposition in this line of White Leghorn laying chickens.

Canine hyperplastic intraepidermal pustular and suprabasal acantholytic dermatosis with features of human pemphigus vegetans.

Pemphigus vegetans is a rare autoimmune blistering acantholytic dermatosis of humans that combines unusually hyperplastic and verrucous pustular skin lesions and mucosal erosions. We report herein the clinical, histopathologic, and immunologic findings in a dog whose lesions resembled, but were not identical to, those of human pemphigus vegetans. A 4-year-old male Greater Swiss Mountain Dog presented with multifocal cutaneous verrucous and crusted papules and pustules, as well as skin and mucosal erosions and ulcers. Microscopic lesions consisted of exophytic papillated epidermal hyperplasia, superficial and deep intraepidermal acantholytic neutrophilic and eosinophilic pustules, and suprabasal epidermal clefts leaving rounded basal keratinocytes at the bottom of the vesicles. Direct and indirect immunofluorescence revealed antikeratinocyte IgG autoantibodies. Immunoprecipitation immunoblotting and immunoabsorption experiments with recombinant canine desmogleins confirmed that autoantibodies recognized desmoglein-1. In this dog, clinical and histopathologic features resembled those of human pemphigus vegetans, while circulating autoantibodies against canine desmoglein-1 were solely identified. This antigen target is different from that of the human disease in which antidesmoglein-3 autoantibodies are detected most commonly.

Idiopathic linear pustular acantholytic dermatosis in a young Brittany Spaniel dog.

A unilateral, linear, papular-pustular dermatosis is described in a young Brittany Spaniel dog. The dermatosis appeared to follow Blaschko's lines and extended from the left inguinal region to the medial aspect of the left metatarsal area. The predominant histological finding was an eosinophilic and neutrophilic pustular mural folliculitis with prominent acantholysis of infundibular epithelium. There was a rapid and long-lasting (> 15 months) resolution after oral administration of methylprednisolone (1.6 mg kg(-1)).

Dominantly inherited epidermal acantholysis in dogs, simulating human benign familial chronic pemphigus (Hailey-Hailey disease).

We report on dominantly inherited epidermal acantholysis in three dogs, a sire and two female offspring. The skin lesions were characterized by hairless, hypertrophic plaques. Histopathologically, these lesions showed epidermal hyperplasia with individual enlargement of keratinocytes, extensive acantholysis and minimal dyskeratosis. Ultrastructural analysis revealed that attachment plaques of desmosomes were still intact while some tonofilaments were detached from them in early lesions; there were well-developed microvilli at dissociated cell surfaces. The data imply that these animals have undergone a process similar to human benign familial chronic pemphigus (BFCP). Immunohistochemical examination revealed that staining for E-cadherin and actin variably remained in dissociated keratinocytes. Focal intracellular staining for desmosomal glycoproteins and desmosomal proteins were observed within the dissociated keratinocytes. This dominantly inherited acantholytic disease in dogs could be a useful animal model for investigating the pathogenesis of BFCP in humans.

Langerhans cells in the development of skin cancer: a qualitative and quantitative comparison of cell markers in normal, acanthotic and neoplastic ovine skin.

The distribution of Langerhans cells in normal, acanthotic and neoplastic ovine epithelium was examined using the enzyme marker Acetylcholinesterase (AchE) and monoclonal antibodies (MoAb) to CD1 (20.27) and MHC Class II (49.1 and 28.1) molecules. In normal skin, where Langerhans cells were regularly spaced within the basal layer, qualitative observations and direct pairwise testing showed that AChE was superior to the MoAb in detecting these cells. Significantly more (P < 0.01) dendritic cells were also detected with MoAb 49.1 than MoAb 20.27 or 28.1, suggesting differential expression of MHC Class II subsets and the presence of CD1- MHC Class II+ granule- dendritic cells in sheep analogous to indeterminate cells of man. In acanthotic skin, compared to normal skin, Langerhans cells were less numerous, irregular and more suprabasal in distribution and their morphology was occasionally swollen and indistinct. No difference was seen in the ability of AChE and MoAb in detecting Langerhans cells, however pairwise testing of markers did demonstrate that significantly more (P < 0.05) cells without dendritic processes were stained with MoAb 49.1 than with 20.27 or 28.1. In all squamous cell carcinomas examined dendritic cells that stained for AChE, CD1 or MHC Class II antigens were concentrated at the peripheral areas of neoplastic epithelium. Many dendritic cells were detected with MoAb to MHC Class II antigens, whereas CD1 and AChE positive dendritic cells were rare in tumor bearing tissue. The quantitative differences in the immunohistochemical staining of Langerhans cells between normal, acanthotic and neoplastic epithelium were consistent with ultrastructural studies. When compared with those of a newborn lamb, which had had very little exposure to antigens or ultraviolet radiation (UVR), the Langerhans cells of the aged sheep were deformed and contained far fewer Birbeck granules. The abnormalities were progressively more severe in acanthotic and neoplastic skin. These observed changes may have resulted from UVR induced damage and may be indicative of impaired function involved in the development of skin cancer.

The distribution of lymphocyte subpopulations in normal and acanthotic ovine skin.

The prevalence and distribution of lymphocyte subpopulations in normal and acanthotic ovine skin were investigated using monoclonal antibody immunocytochemistry. CD8+ cells were predominant in the epidermis of both normal and acanthotic skin, but were CD8+ cells, CD4+ cells and T19+ cells infrequent in normal epidermis. Within the dermis of normal skin, there were significantly greater numbers of CD4+ and T19+ cells situated around the superficial dermal vessels than in any other region examined. The majority of the CD8+ cells adjoined vessels, but the proportion that did not was greater for CD8+ than for CD4+ or T19+ cells. The CD4+ and CD8+ subsets were represented equally in adnexa. T cells were of memory phenotype. B cells and naive T cells, both of which express the CD45RA antigen, were rarely seen and tended to be associated with vessels in both normal and acanthotic skin. None of the T19+ cells (which are gamma delta+) resembled the dendritic gamma delta cells seen in murine epidermis. Acanthotic skin was strikingly different to normal skin. There was a greater abundance of T cells, particularly CD4+ cells, in acanthotic epidermis and the numbers of CD8+ and T19+ cells, and to a greater extent CD4+ cells, were greater at the dermal-epidermal junction. There were more CD4+ and CD8+ cells in the superficial dermal stroma of acanthotic skin. Within the dermis of acanthotic skin, T cells were concentrated near vessels but the apportioning of T cells between stromal/adnexal and vessel-associated sites differed from normal. Such observations suggest that migration away from perivascular sites and into the stroma may be controlled separately for subregions of skin and for each T cell subset. The role of this altered nonrandom migration of T cells in skin chronically exposed to ultra violet radiation is uncertain.

Comparative histopathology of pemphigus foliaceus and superficial folliculitis in the dog.

A comparative histopathologic study of 50 cases of pemphigus foliaceus and 47 cases of superficial folliculitis in the dog was undertaken to identify those histopathologic features important in differentiating these diseases. All cases were diagnosed by the Surgical Pathology Service of the Laboratory of Pathology of the University of Pennsylvania, School of Veterinary Medicine, between January 1986 and March 1991. These cases were followed clinically to determine the accuracy of the initial histopathologic diagnosis. Data were analyzed by Fisher's exact test for discrete data and the Mann-Whitney U-test for continuous data. A probability of < 0.05 was considered statistically significant. The following breeds were affected with pemphigus foliaceus: Akita, Brittany Spaniel, Chow Chow, Collie, Dachshund, Doberman Pinscher, English Cocker Spaniel, English Setter, Golden Retriever, Siberian Husky, Laborador Retriever, Miniature Schnauzer, Old English Sheepdog, Scottish Terrier, Chinese Shar Pei, Spitz, Shetland Sheep Dog, Weimeraner, and West Highland White Terrier. An increased risk of developing pemphigus foliaceus was noted in the Akita (OR = 37.8), English Springer Spaniel (OR = 20.7), Chow Chow (OR = 12.3), Chinese Shar Pei (OR = 7.9), and Collie (OR = 3.9). Pemphigus foliaceus had a higher average density of acantholytic cells (226 +/- 22.9) than superficial folliculitis (11.8 +/- 4.6), and acantholytic cells were 183 times more likely to be present in pemphigus foliaceus. The presence of rafts of acantholytic cells occurred in pemphigus foliaceus (23/50) more often than superficial folliculitis (1/47). Recornification and reformation of pustules were, respectively, 13.4 and 3.6 times more likely to occur in pemphigus foliaceus.(ABSTRACT TRUNCATED AT 250 WORDS)

The comparative pathology of non-viral bullous skin diseases in domestic animals.

In a review of non-viral bullous skin diseases of domestic animals and a 4-year study of cases presented to the New York State College of Veterinary Medicine, we found 15 diseases: pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, pemphigus erythematosus, bullous pemphigoid, systemic lupus erythematosus, dermatitis herpetiformis, toxic epidermal necrolysis, drug eruption, epidermolysis bullosa, epidermolysis bullosa simplex, familial acantholysis, bovine congenital porphyria, impetigo and subcorneal pustular dermatosis. The 15 diseases were placed in five categories: autoimmune, immune-mediated, hereditary, bacterial and idiopathic. A histologic classification of these disorders based on the site of blister formation and other important clinicopathologic, histologic and immunopathologic findings was developed.

A mucocutaneous disease in the dog, resembling pemphigus vulgaris in man.

A chronic mucocutaneous disease was diagnosed in 3 dogs. Clinically, the disease was characterized by erosions and ulcerations of the oral mucosa, various mucocutaneous junctions, and the skin. Histologically, there was acantholysis or a separation of the epithelial cells from one another, resulting in the formation of clefts and bullae. Based on clinical and laboratory findings, the disease seemed to be the canine equivalent of pemphigus vulgaris (PV) in man.

A disease in dogs resembling human pemphigus vulgaris: case reports.

A pemphigus-like disease occurred in 5 dogs. The canine disease closely resembled pemphigus vulgaris in man and was characterized by ulcerative lesions in the oral cavity, on the skin, and at mucocutaneous junctions. Histologically, the first sign of the disease was disappearance of the intercellular bridges in the lower epidermis. The resulting acantholysis was diagnostic for pemphigus. Antibodies to the intercellular space substance were detected by immunofluorescent staining in serum of 4 of the dogs. High doses of corticosteroids were effective in controlling the disease.